Low-intensity focused ultrasound to the posterior insula reduces temporal summation of pain
Alexander In, Andrew Strohman, Brighton Payne, Wynn Legon
Brain Stimulation 2024, 17, 911-924 · 10.1016/j.brs.2024.07.020
Abstract
Background The insula and dorsal anterior cingulate cortex (dACC) are core brain regions involved in pain processing and central sensitization, a shared mechanism across various chronic pain conditions. Methods to modulate these regions may serve to reduce central sensitization, though it is unclear which target may be most efficacious for different measures of central sensitization. Objective/hypothesis Investigate the effect of low-intensity focused ultrasound (LIFU) to the anterior insula (AI), posterior insula (PI), or dACC on conditioned pain modulation (CPM) and temporal summation of pain (TSP). Methods N = 16 volunteers underwent TSP and CPM pain tasks pre/post a 10 min LIFU intervention to either the AI, PI, dACC or Sham stimulation. Pain ratings were collected pre/post LIFU. Results Only LIFU to the PI significantly attenuated pain ratings during the TSP protocol. No effects were found for the CPM task for any of the LIFU targets. LIFU pressure modulated group means but did not affect overall group differences. Conclusions LIFU to the PI reduced temporal summation of pain. This may, in part, be due to dosing (pressure) of LIFU. Inhibition of the PI with LIFU may be a future potential therapy in chronic pain populations demonstrating central sensitization. The minimal effective dose of LIFU for efficacious neuromodulation will help to translate LIFU for therapeutic options.
Abstract via europepmc.
Exposures
Exposure 1: LIFU to anterior insula (AI)
Target: anterior insula — “anterior insula (AI)”
Device: Sonic Concepts · Sonic Concepts · H-281 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.36 | ✓?⚑ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 36pulse duration × PRF gives 36% | ✓✓✓ |
| Sonication duration (s) | 1 | ✓✓✓ |
| Free-field pressure (kPa) | 380 | ✓✓✓⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | 4.2 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 1.5 | ✓✓✓ |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | 180.1 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
LIFU was applied for 100 stimulations (each a 1 s pulse gated at 1 kHz PRF with 36% duty cycle) separated by a fixed inter-stimulus interval of 5 s, for a total application time of 10 min; this gives a final average duty cycle of 6% over the 10 min of sonication.
Exposure 2: LIFU to posterior insula (PI)
Target: posterior insula — “posterior insula (PI)”
Device: Sonic Concepts · Sonic Concepts · H-281 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.36 | ✓? |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 36pulse duration × PRF gives 36% | ✓✓✓ |
| Sonication duration (s) | 1 | ✓✓✓ |
| Free-field pressure (kPa) | 380 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 4.2 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 1.5 | ✓✓✓ |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | 262.1 | ✓✓✓ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
LIFU was applied for 100 stimulations (each a 1 s pulse gated at 1 kHz PRF with 36% duty cycle) separated by a fixed inter-stimulus interval of 5 s, for a total application time of 10 min; this gives a final average duty cycle of 6% over the 10 min of sonication.
Exposure 3: LIFU to dorsal anterior cingulate cortex (dACC)
Target: dorsal anterior cingulate cortex — “dorsal anterior cingulate cortex (dACC)”
Device: Sonic Concepts · Sonic Concepts · H-104 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.36 | ✓? |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 36pulse duration × PRF gives 36% | ✓✓✓ |
| Sonication duration (s) | 1 | ✓✓✓ |
| Free-field pressure (kPa) | 400 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 4.5 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 1.62 | ✓✓✓ |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | 119.8 | ✓✓✓ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
LIFU was applied for 100 stimulations (each a 1 s pulse gated at 1 kHz PRF with 36% duty cycle) separated by a fixed inter-stimulus interval of 5 s, for a total application time of 10 min; this gives a final average duty cycle of 6% over the 10 min of sonication.
Flags from extraction
exposures[0].free_field.pressure_kpa— Paper calls this the 'applied external pressure' calibrated from free-water test-tank measurements; it is not explicitly labelled 'free field', so the domain assignment is inferred from the methods description of free-water beam calibration.exposures[0].timing.pulse_duration_ms— Pulse duration (0.36 ms) is derived from the stated duty cycle (36%) and PRF (1 kHz) per the burst rule, since the paper does not separately state the on-time of the 1 kHz-gated sub-pulse.exposures[0].in_situ.pressure_kpa— Simulated intracranial pressure is a group mean ± SD across N=16 participants; SD is in the quote.